Gene Expression Of FASN Research Articles

The molecular signature of cumulus cells is compromised in infertile women of advanced maternal age

It is well known that women in their forties experience a decline in their fertility. Compromised folliculogenesis leading to poor oocyte quality contributes to a reduction in implantation potential. This study investigated the molecular signature of cumulus cells from infertile women in their early-mid forties relative to young fertile oocyte donors. Research study Patients donated with consent cumulus cells during routine IVF treatment: Group A = young fertile oocyte donors (n = 20) and Group B = infertile normal responders with normal ovarian reserve in their early-mid forties (n = 28). Proteomic analysis of pooled cumulus cells involved liquid chromatography tandem mass spectrometry (LC-MS) and Western blotting. Cumulus cell gene expression analysis was performed by quantitative real-time PCR relative to a constant housekeeping gene. LC-MS identified 1423 proteins across these cumulus cell samples. Statistical analysis revealed 64 proteins with increased expression in Group B, including proteins involved in fatty acid metabolism e.g., ACAT2 and HSD17B4 (P<0.05; >1.5 fold change). In addition, 48 proteins showed decreased expression in Group B, including pre-mRNA splicing factors e.g., KHSRP, SFPQ and DDX46 (P<0.05; >1.5 fold change). Western blotting successfully validated the LC-MS data confirming differential expression of ACAT2, KHSRP, SFPQ and DDX46. Cumulus cell gene expression of ACAT2, HSD17B4, ACSL3, CPT2, SCD and FASN further confirmed the up-regulation of fatty acid metabolism genes relative to infertility and maternal aging (P<0.05). In a novel approach, this study examined protein and gene expression of cumulus cells with respect to infertility and maternal age. A compromised molecular environment was observed with a deficiency in pre-mRNA splicing factors and increased fatty acid metabolism in infertile aged cumulus cells. Investigation of these pathways may contribute to improvements in patient care and success for infertile women in their forties.

Fat Oxidation, Fitness and Skeletal Muscle Expression of Oxidative/Lipid Metabolism Genes in South Asians: Implications for Insulin Resistance?

BackgroundSouth Asians are more insulin resistant than Europeans, which cannot be fully explained by differences in adiposity. We investigated whether differences in oxidative capacity and capacity for fatty acid utilisation in South Asians might contribute, using a range of whole-body and skeletal muscle measures.Methodology/Principal FindingsTwenty men of South Asian ethnic origin and 20 age and BMI-matched men of white European descent underwent exercise and metabolic testing and provided a muscle biopsy to determine expression of oxidative and lipid metabolism genes and of insulin signalling proteins. In analyses adjusted for age, BMI, fat mass and physical activity, South Asians, compared to Europeans, exhibited; reduced insulin sensitivity by 26% (p = 0.010); lower VO2max (40.6±6.6 vs 52.4±5.7 ml.kg−1.min−1, p = 0.001); and reduced fat oxidation during submaximal exercise at the same relative (3.77±2.02 vs 6.55±2.60 mg.kg−1.min−1 at 55% VO2max, p = 0.013), and absolute (3.46±2.20 vs 6.00±1.93 mg.kg−1.min−1 at 25 ml O2.kg−1.min−1, p = 0.021), exercise intensities. South Asians exhibited significantly higher skeletal muscle gene expression of CPT1A and FASN and significantly lower skeletal muscle protein expression of PI3K and PKB Ser473 phosphorylation. Fat oxidation during submaximal exercise and VO2max both correlated significantly with insulin sensitivity index and PKB Ser473 phosphorylation, with VO2max or fat oxidation during exercise explaining 10–13% of the variance in insulin sensitivity index, independent of age, body composition and physical activity.Conclusions/SignificanceThese data indicate that reduced oxidative capacity and capacity for fatty acid utilisation at the whole body level are key features of the insulin resistant phenotype observed in South Asians, but that this is not the consequence of reduced skeletal muscle expression of oxidative and lipid metabolism genes.

Inverse relation between FASN expression in human adipose tissue and the insulin resistance level

BackgroundAdipose tissue is a key regulator of energy balance playing an active role in lipid storage and may be a dynamic buffer to control fatty acid flux. Just like PPARγ, fatty acid synthesis enzymes such as FASN have been implicated in almost all aspects of human metabolic alterations such as obesity, insulin resistance or dyslipemia. The aim of this work is to investigate how FASN and PPARγ expression in human adipose tissue is related to carbohydrate metabolism dysfunction and obesity.MethodsThe study included eighty-seven patients which were classified according to their BMI and to their glycaemia levels in order to study FASN and PPARγ gene expression levels, anthropometric and biochemical variables.ResultsThe main result of this work is the close relation between FASN expression level and the factors that lead to hyperglycemic state (increased values of glucose levels, HOMA-IR, HbA1c, BMI and triglycerides). The correlation of the enzyme with these parameters is inversely proportional. On the other hand, PPARγ is not related to carbohydrate metabolism.ConclusionsWe can demonstrate that FASN expression is a good candidate to study the pathophysiology of type II diabetes and obesity in humans.